What are the evidence based treatments of painful distal symmetric polyneuropathy and small fiber neuropathy?
Nearly all evidence-based treatments are based upon studies performed in people with diabetic neuropathy. There is a strong evidence base for the efficacy of tricyclic agents (principally amitriptyline) pregabalin, gabapentin, and SNRIs (principally duloxetine). Some evidence also exists for efficacy of opioids in neuropathic pain, but these are not considered first-line therapies for neuropathic pain states. Many other agents have been investigated with equivocal evidence to support their use.
Among topical agents, only one, 0.1% clonidine gel, has been shown to be beneficial among patients with paraclinical evidence of some preserved small fiber function.
For unclear reasons, HIV infection and chemotherapy are two etiologies of painful neuropathy that tend to be particularly refractory to treatment. A 30-minute application of high-potency (8%) capsaicin has demonstrated statistically meaningful benefit for neuropathic pain from HIV, but is not FDA approved for this indication.